Supramolecular Gel Control of Cisplatin Crystallization: Identification of a New Solvate Form Using a Cisplatin-Mimetic Gelator

A series of platinum based low-molecular-weight
urea-based gelators C1, C2, and C3, mimicking the structure
of the anticancer drug cisplatin has been synthesized, as part of
the development of a targeted, supramolecular gel phase crystallization
and polymorphism screening strategy. Morphological and rheological
studies established that inclusion of a longer spacer between the
urea and cisplatin-mimetic regions of the gelator (C3) resulted in optimal gelation performance. Interfacial crystallization
of cisplatin in a gel–sol biphasic system has been employed
to address the insolubility of the drug molecule in organic solvents.
A new N,N-dimethylacetamide (DMA) solvate of cisplatin
has been identified and a crystal habit modification of the known N,N-dimethylformamide (DMF) solvate form of cisplatin has
been observed on crystallization of cisplatin in C3 gels
prepared in xylenes. While both targeted and nontargeted gels resulted
in the formation of the new DMA solvate, only the targeted C3 gel resulted in high-quality single crystal suitable for characterization
by single crystal crystallography. The high crystal quality is attributed
to a close match between the core geometry of C3 with
that of cisplatin together with local order in the gel fibers of C3.

为开发靶向性超分子凝胶相结晶与多态性筛选策略，本研究合成了一系列模拟抗癌药物顺铂（cisplatin）结构的铂基低分子量脲基凝胶因子C1、C2与C3。形貌与流变学研究表明，在凝胶因子C3的脲基区域与顺铂模拟区域之间引入更长的连接臂，可使其凝胶性能达到最优。本研究采用凝胶-溶胶双相体系中的顺铂界面结晶法，以解决该药物分子在有机溶剂中难溶的问题。本研究首次发现了顺铂的一种新型N,N-二甲基乙酰胺（DMA）溶剂化物，并在以二甲苯制备的C3凝胶中进行顺铂结晶时，观察到了已知顺铂N,N-二甲基甲酰胺（DMF）溶剂化物的晶习改变现象。尽管靶向与非靶向凝胶体系均可生成新型DMA溶剂化物，但仅靶向性C3凝胶可得到适用于单晶晶体学表征的高质量单晶体。该高晶体质量可归因于两点：一是C3的核心几何结构与顺铂高度匹配，二是C3凝胶纤维中存在局部有序排列。